Synthesis and Antifungal Activity of N-(3-(4-(1,3-dioxolan-2-yl) phenyl)- 1,2,4-thiadiazol-5-yl) Benzamide Derivatives: An in-vitro Study

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Introduction: Fungal infections are associated with morbidity and mortality globally and immense economic burden. With the emergence of multidrug resistant fungal strains, it is essential to develop new antifungal drugs. Aim: To synthesize and evaluate the antifungal activity of N-(3- (4-(1,3-dioxolan-2-yl) phenyl)-1,2,4-thiadiazol-5-yl) benzamides against Candida albicans, Cryptococcus neoformans and Aspergillus niger. Materials and Methods: An in-vitro study was conducted in the Department of Chemistry, Islamiah College, Vaniyambadi, Tamil Nadu, India from August 2022 to February 2024. Novel N-(3-(4-(1,3-dioxolan-2-yl) phenyl)-1,2,4-thiadiazol-5-yl) benzamides were synthesized by a simple procedure. Pyridine was added to 3-(4-(1,3-dioxolan-2yl) phenyl)-1,2,4-thiadiazol-5- amine and dichloromethane was added dropwise. The resulting mixture was washed with water, saturated brine solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The purification of crude residue was done by column chromatography. Their characteristics were confirmed by 1H and 13C Nuclear Magnetic Resonance (NMR) and Liquid Chromatography- Mass Spectrometry (LC-MS). They were screened for activity against Candida albicans, Cryptococcus neoformans and Aspergillus niger by disc diffusion method. A loopful of cells from fungal stock cultures was added to Sabouraud Dextrose Broth (SDB) containing test tubes and incubated at 25°C for 24 hours. The experiments were conducted with the test compounds and control experiment was done with Fluconazole. The growth inhibition zones around the disks were measured in mm at 28°C after 2-3 days. Results: Twelve N-(3-(4-(1,3-dioxolan-2-yl) phenyl)-1,2,4- thiadiazol-5-yl) benzamides (7a-7l) were synthesized with good yield. Compounds 7c and 7g had good activity against Candida albicans. Compounds 7f and 7g had moderate activity against Aspergillus niger, whereas Compounds 7d, 7f and 7h had moderate activity against Cryptococcus neoformans. Conclusion: A series of N-(3-(4-(1,3-dioxolan-2-yl) phenyl)- 1,2,4-thiadiazol-5-yl) benzamides (7a-7l) were synthesized. These compounds have moderate to good antifungal activity against Candida albicans, and moderate activity against Aspergillus niger and Cryptococcus neoformans.